Protocadherin 19 (PCDH19) female limited epilepsy (PCDH19-FE; also known as epilepsy and mental retardation limited to females, EFMR; MIM300088) is an infantile onset epilepsy syndrome with or without intellectual disability (ID) and autism.
The present findings confirm that PCDH19 is a major causative gene for infantile onset familial or sporadic epilepsy in female patients with or without mental retardation.
Other types of seizures were found in both epilepsies with a prevalence of GTCS and atypical absences in DS, and focal motor and hypomotor seizures in PCDH19-related epilepsy.
Overall our initial characterization of Pcdh19(+/β-Geo), Pcdh19(β-Geo/β-Geo) and Pcdh19(Y/β-Geo)mice reveals that despite widespread expression of Pcdh19 in the CNS, and its role in human epilepsy, its function in mice is not essential for brain development.
We report a retrospective multicenter study of antiepileptic therapy in 58 female patients with PCDH19 mutations and epilepsy aged 2-27 years (mean age 10.6 years).
In addition, we show that several PCDH19-FE missense mutations localize to the adhesive interface and abolish Pcdh19 adhesion in <i>in vitro</i> assays, thus revealing the biochemical basis of their pathogenic effects during brain development.
Additionally, a heterozygous c.2926G>A (Asp976Asn) of PCDH19 was identified in patient with PIGV mutations, the causative gene of Epilepsy and mental retardation limited to females (EFMR).
This PCDH19-NONO-ERα axis is of relevance not only to PCDH19-epilepsy and its comorbidities but likely also to ERα and generally nuclear hormone receptor-associated cancers.
The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated.
Our results highlight the role of PCDH19 in determining cell adhesion affinities during cortical development and the way segregation of WT and null PCDH19 cells is associated with the unique X-linked inheritance of PCDH19epilepsy.
We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers.
We described three variations in the PCDH19 gene in Chinese patients with epilepsy who developed generalized seizures occurring in clusters with or without triggering by fever.